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Corporate Presentation

Corporate Presentation. July 2013. Safe Harbor Statement.

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Corporate Presentation

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  1. Corporate Presentation July 2013

  2. Safe Harbor Statement • During the course of this presentation we will make statements that constitute forward-looking statements. These statements may include operating expense projections, the initiation, timing and results of pending or future clinical trials, the actions or potential action of the FDA, the status and timing of ongoing research, corporate partnering activities and other factors affecting Adherex Technologies’ financial condition or operations. Such forward looking statements are not guarantees of future performance and involve risk, uncertainties and other factors that may cause actual results, performance or achievements to vary materially from those expressed or implied in such statements. These and other risk factors are listed from time to time in reports filed with the SEDAR and the Securities and Exchange Commission, including but not limited to, reports on Forms 10-Q and 10-K. Adherex does not intend to update any forward looking information to reflect actual results or changes in the factors affecting forward-looking information.

  3. Fluorouracil Market Overview • 5-FU (5-Fluorouracil) • Discovered in 1957, widely available as generic • IV only • Principal uses: colorectal, breast, gastric, pancreatic, head and neck, ovarian and basal cell cancer • Used in combination with leucovorin, which improves 5-FU antitumor activity • Annual use: 500,000 patients in North America, millions worldwide • Xeloda®(capecitabine) Oral, prodrug of 5-FU On the market since 1998, expected generic in the US by 2013/2014 Principal uses: colorectal, breast and gastric cancer Not used with leucovorin Global Sales in 2012 of $1.6B 12% YOY growth, $634 MM US Sales, marketed by Roche • UFT® (tegafur-uracil) • Developed in Japan during the 1980s • Oral, combining uracil (competitive inhibitor of DPD) and tegafur (prodrug of 5-FU) • Approved in 50 countries, except the US • Principal uses: colorectal, breast, gastric, pancreatic, head and neck, liver, ovarian and basal cell cancer • Used in combination with leucovorin • Marketed by Merck Serono, Korea United and Taiho • Teysuno® • (tegafur-gimeracil-oteracil-potassium) Oral combination of tegafur (prodrug of 5-FU) plus 2 enzyme inhibitors: gimeracil and oteracil On the market since 1999 in Japan and since 2011 in Europe, marketed by Taiho Principal uses: gastric, colorectal, head and neck, non-small cell lung, breast, pancreatic cancer Not used with leucovorin

  4. Lead Product Candidate: Eniluracil Oral Chemotherapy for Solid Tumors Irreversible inhibitor of DPD, the enzyme responsible for the rapid breakdown of 5-FU Developed as a potentiator of 5-FU in the 1990s by Burroughs Wellcome and then by GlaxoWellcome (now GSK)

  5. 5-FU Metabolic Pathways • 5-FU must be activated to kill cancer cells • The enzyme, DPD, prevents activation and degrades 5-FU to F-BAL • DPD problems: • Highly Variable levels • Unpredictable 5-FU PK • 5-FU t1/2 = 10-20 min • 5-FU MTD correlates with DPD • F-BAL problems: • >80% of dose = F-BAL • Decreases 5-FU Efficacy • Neurotoxic • Hand-foot syndrome (HFS) agent (PK = pharmacokinetics; measurements of 5-FU in patient’s blood. MTD = Maximum Tolerated Dose)

  6. The Solution: EU Inactivates DPD • EU Eliminates DPD & F-BAL Problems • 5-FU is not destroyed: • Half-life = 5 hr. • Highly predictable linear PK • Oral dosing • F-BAL formation is minimal: • No interference with efficacy • Minimize neurotoxicity • HFS is negligible

  7. High EU:5-FU Ratio Decreases Efficacy In a study of rats with large tumors: EU:5-FU ratio 5:1 ratio excess EU present <1:5 ratio excess EU avoided Data: Spector T, Cao, S. A Possible Cause and Remedy for the Clinical Failure of 5-Fluorouracil plus Eniluracil. Clinical Colorectal Cancer. 2010;9(1):52-4. A high ratio of EU to 5-FU was less effective than a low ratio

  8. EncouragingComparison Dr. Grem’s Phase I Weekly Schedule vs. Xeloda®’s Phase 2 in Advanced Colorectal Cancer Refractory to iv 5-FU/Lv Eniluracil/5-FU/leucovorin: better efficacy and less toxicity than Xeloda® This study established the correct 5-FU dose, without excess EU

  9. Phase 2 Oral 5-FU Regimens Modified weekly EU/5-FU/Lv schedule (all oral regimen) Administers a higher EU dose to eliminate all DPD, including DPD in nervous tissue to minimize neurotoxicity. Allows excess EU to be cleared before dosing with 5‑FU Administers 5‑FU when the EU:5‑FU ratio is very low to optimize efficacy Administers Lv with 5‑FU and 24 hr afterwards to potentiate 5-FU efficacy Described in Adherex use patents issued and pending worldwide, expiring from 2025 to 2029 Arm 1: Modified WeeklySchedule: taken 3 weeks followed by 1 week interlude 5-FU Dose: 30 mg/m2 EU:5-FU will be ≤ 1:10+ Leucovorin Dose: 30 mg EU Dose: 40 mg (11-16 hr before 5-FU) LeucovorinDose: 30 mg Arm 2: 1000 mg/m2 Xeloda® twice daily for 14 days followed by 7 days interlude

  10. Phase 2 Study Design Other Reasons Arm 1 80 Subjects EU/ 5-FU / Lv Randomization: N = 140: first- or second-line therapy for MBC patients who had previous treatment with an anthracycline and a taxane PD Assessment of Primary Endpoint: Progression-Free Survival X-over Option PD Arm 2 60 Subjects Xeloda® Other Reasons Arm 1: Eniluracil/5-FU/leucovorin Arm 2: Xeloda® (capecitabine) X-over: Crossover Group Analyzed Separately Treat and assess as Per Protocol Stop treatment because of: Continue to treat and assess

  11. Interim Study Efficacy Results* Arm 1: EU/5-FU/Lv vs. Arm 2: Xeloda® Arm X: patients who failed Xeloda®and crossed over to take EU/5-FU/Lv *All data as of March 30, 2013 1. Clinical benefit: CR=Complete Response, PR =Partial Response, SD=Stable Disease 2. Subjects who progressed (PD) on Arm 2 Xeloda within 70 days (<one scan) 3. Subjects who progressed (PD) on Arm 2 Xeloda after 70 days (>one scan)

  12. Main Study PFS Interim Results Arm 1: EU/5-FU/Lv vs. Arm 2: Xeloda® (capecitabine)

  13. Arm 2 Patients Who Rapidly Failed Xeloda®and Crossed Over to Take EU/5-FU/Lv in Arm X Unexpected Activity in Arm X *Patient withdrew from study to have surgery after a SD assessment

  14. Crossover Arm PFS in Rapid Xeloda Failures Arm 2: Xeloda® (capecitabine) vs. Arm X: EU/5-FU/Lv

  15. Serious Adverse Events* • *All data as of March 30, 2013 • aAll three events were in the same patient

  16. Interim Adverse Events* *Patients were assessed 3 times per cycle in the EU/5-FU/Lv arm and only once per cycle in the Xeloda arm, which may account for the higher incidence of some of the findings in the EU/5-FU/Lv arm.

  17. EU/5-FU/Lv clinical benefit vs Xeloda® The possible mechanisms for rapid Xeloda® failure and subsequent clinical benefit from EU/5-FU/Lv may include any of the following: Low Xeloda® absorption (highly variable with possible extended lag periods) Low or deficient levels of one or more of the three enzymes required to convert Xeloda® to 5-FU Low intratumoral thymidine phosphorylase Elevated DPD Up to 85-fold swings in the diurnal variation of DPD levels F-Bal interfering with the antitumor activity Added benefit of leucovorin EU/5-FU/Lv circumvents and/or eliminates problems 1-6 and enables the safer use of leucovorin because EU creates consistent and predictable 5-FU pharmacokinetics

  18. EU/5-FU/Lv Advantages vsTeysuno® and UFT ® DPD inhibitor (5-Chloro, 2,4- dihydroxypyridine) used in Teysuno®(S-1) is a simple competitive reversible inhibitor. Accordingly, it must be present when 5-FU is administered to inhibit 5-FU breakdown by DPD.  Therefore, it is likely to interfere with the antitumor activity of 5-FU in a similar manner that excess eniluracil interferes. Because eniluracil is an irreversible inactivator of DPD, it can be dosed the night before 5-FU and cleared from the body before 5-FU is dosed. Therefore, it is not present to interfere with 5-FU antitumor activity. Because eniluracil eliminates all DPD, the 5-FU PK are remarkably consistent and predictable, thereby allowing the safe use of leucovorin to potentiate the antitumor activity of 5-FU In contrast, the variable conversion of the tegafurprodrug to 5-FU and its variable breakdown by DPD result in variable 5-FU PK from S-1, which render co-administration of leucovorin risky. UFT ® has uracil as the DPD inhibitor.  Uracil and thymine are the natural substrates for DPD. Uracil only inhibits as it is being degraded by DPD.  It's a weak, reversible, alternative-substrate inhibitor that is metabolically depleted by DPD.  Head-to-head in rats, EU/5-FU was considerably better than UFT.

  19. FDA EOP 2 Meeting Summary Interim Results indicate EU/5-FU/Lv regimen active and well tolerated in MBC FDA can not endorse a single arm pivotal trial in rapidly failed Xeloda®patients since there are other approved therapies available such as Halaven®andIxempra® Discussed with Adherex the following development options in MBC: One superiority study vsXeloda®monotherapy for 1st or 2nd line therapy in metastatic setting for patients previously treated with an anthracyclene and a taxane One superiority study vs physician’s drug of choice for patients who have previously received at least two chemotherapeutic regimens in metastatic setting and were previously treated with an anthracycline and a taxane Two non inferiority studies vs physician’s drug of choice for patients who have previously received at least two chemotherapeutic regimens in metastatic setting and were previously treated with an anthracycline and a taxane Adherexmust demonstrate the contribution of Leucovorin in future MBC studies, but not in colorectal cancer (CRC) where Leucovorin is approved Historical Eniluracil safety database supports future NDA filing FDA encourages Adherex to meet again and discuss a trial design for future Phase 3 study

  20. EU/5-FU/Lv Development Plan Future studies of EU/5-FU/Lv regimen in MBC require very large number of patients EU/5-FU/Lvactive and well tolerated in refractory iv 5-FU and Xeloda® populations Encouraging results from Dr. Grem Phase I study in mCRC and Adherex Phase 2 study in MBC Discussing with Dr. Howard Hochster from Yale the following development options in mCRC: One superiority study vsregorafenib (Stivarga® ) for patients who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild-type, an anti-EGFR therapy One superiority study vs placebo for patients who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, regorafenib and, if KRAS wild-type, an anti-EGFR therapy Patients have short expected overall survival making a smaller improvement more meaningful Possibly fast enrolling trial, could be done in the US Enthusiastic investigators, sites and PI have been identified A single Phase 3 adaptive trial could lead to approval Adherex is seeking a partnership to advance this plan forward

  21. Eniluracil Summary Eniluracilis active and well tolerated Indications where 5-FU is administered potentially in excess of $1 BLN market Seek partnership for further development of Eniluracil

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